Clinicopathological correlation of patients with lupus nephritis: Data from a tertiary center in Saudi Arabia.

Systemic lupus erythematosus mainly affects young women, and approximately half of systemic lupus erythematosus patients develop lupus nephritis (LN). However, data on the types and remission rates of LN in Saudi Arabia are limited. Therefore, we aimed to highlight the LN remission rates in our population. A retrospective record review was conducted between January 2007 and December 2020 in a tertiary center in the western region of Saudi Arabia to determine the remission rates among patients with biopsy-proven LN who met the EULAR\ACR 2019 classification criteria. We identified 59 patients with biopsy-proven LN, mostly in young women. The common histopathological pattern was Class IV LN in 26 patients (44%). Three induction protocols were identified, along with systemic steroids: the high-dose cyclophosphamide protocol in 21 patients (35.6%), low-dose protocol in 4 patients (6.8%), and mycophenolate mofetil (MMF) in 41 patients (69.5%). Partial response, defined as the reduction of the 24-hour proteinuria by 25% at 3 months and 50% at 6 months, was achieved in 18 patients (33.3%) at 3 months and decreased to 13 patients (24.1%) at 6 months. Complete clinical response, defined as 24-hour urinary protein between 500 and 700 mg at 12 months, was achieved in 44 patients (81.5%). Complete remission was higher among patients with Class IV LN (64.4%). The achievement of partial clinical response at 3 months was significantly lower among patients with hypertension (P = .041). This study presented the LN remission rates in a single center in Saudi Arabia. Similar to previous studies, Class IV LN were the most common histopathological finding in this study. Complete remission at 12 months was achieved in 44 (81%) patients. Delayed remission is associated with hypertension at the time of LN diagnosis.

Evaluating inter-rater reliability in the context of "Sysmex UN2000 detection of protein/creatinine ratio and of renal tubular epithelial cells can be used for screening lupus nephritis": a statistical examination.

BACKGROUND: The evaluation of inter-rater reliability (IRR) is integral to research designs involving the assessment of observational ratings by two raters. However, existing literature is often heterogeneous in reporting statistical procedures and the evaluation of IRR, although such information can impact subsequent hypothesis testing analyses. METHODS: This paper evaluates a recent publication by Chen et al., featured in BMC Nephrology, aiming to introduce an alternative statistical approach to assessing IRR and discuss its statistical properties. The study underscores the crucial need for selecting appropriate Kappa statistics, emphasizing the accurate computation, interpretation, and reporting of commonly used IRR statistics between two raters. RESULTS: The Cohen's Kappa statistic is typically used for two raters dealing with two categories or for unordered categorical variables having three or more categories. On the other hand, when assessing the concordance between two raters for ordered categorical variables with three or more categories, the commonly employed measure is the weighted Kappa. CONCLUSION: Chen and colleagues might have underestimated the agreement between AU5800 and UN2000. Although the statistical approach adopted in Chen et al.'s research did not alter their findings, it is important to underscore the importance of researchers being discerning in their choice of statistical techniques to address their specific research inquiries.

Evaluation of Type 2 SLE symptoms in patients with a range of lupus nephritis activity.

BACKGROUND: Type 2 systemic lupus erythematosus (SLE) symptoms, including fatigue, fibromyalgia, and brain fog, contribute to poor health-related quality of life (HRQoL) in patients with lupus. To test the hypothesis that Type 1 (classical inflammatory lupus) activity is associated with Type 2 SLE activity, we characterized the features of Type 2 SLE in patients with a range of lupus nephritis (LN) activity. METHODS: This was a cross-sectional study of SLE patients [American College of Rheumatology (ACR) 1997 or Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria] from June 2018 to March 2020. Patients completed the Systemic Lupus Activity Questionnaire (SLAQ) and the Polysymptomatic Distress Scale. Patients were divided into groups based on their renal status. Active nephritis was defined using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) lupus nephritis parameter. Differences across groups were analyzed by Fisher's exact test and ANOVA. RESULTS: In this cohort of 244 patients (93% female, mean age 43 years, 58% Black), 10% had active nephritis, 35% had historical nephritis, and 55% never had nephritis (non-nephritis). Active nephritis and non-nephritis patients had a similar burden of Type 2 SLE symptoms, despite a difference in Type 1 SLE activity. Patients with active nephritis had higher Type 2 PGA (Physician Global Assessment) scores and reported more Type 2 SLE symptoms than inactive nephritis patients. Patients with inactive nephritis had the lowest Type 2 SLE activity. CONCLUSIONS: While Type 2 SLE symptoms are common in SLE, our findings suggest that patients with active nephritis experience significant Type 2 SLE symptoms that may be ameliorated as nephritis improves. We also observed that non-nephritis patients had a similar burden of Type 2 SLE symptoms as patients with active nephritis, despite having on average lower Type 1 SLE activity. Therefore, the etiology of Type 2 SLE symptoms is likely multifactorial and may be driven by inflammatory and non-inflammatory biopsychosocial factors. Key Points • Patients with active nephritis experienced significant Type 2 symptoms that may be ameliorated as nephritis improves. • Non-nephritis patients had a similar burden of Type 2 SLE symptoms as patients with active nephritis, despite having on average lower Type 1 SLE activity. • Because etiology of Type 2 SLE symptoms is likely multifactorial and may be driven by inflammatory and non-inflammatory biopsychosocial factors.

Prediction of treatment response in lupus nephritis using density of tubulointerstitial macrophage infiltration.

Background: Lupus nephritis (LN) is a common disease with diverse clinical and pathological manifestations. A major challenge in the management of LN is the inability to predict its treatment response at an early stage. The objective of this study was to determine whether the density of tubulointerstitial macrophage infiltration can be used to predict treatment response in LN and whether its addition to clinicopathological data at the time of biopsy would improve risk prediction. Methods: In this retrospective cohort study, 430 patients with LN in our hospital from January 2010 to December 2017 were included. We used immunohistochemistry to show macrophage and lymphocyte infiltration in their biopsy specimens, followed by quantification of the infiltration density. The outcome was the treatment response, defined as complete or partial remission at 12 months of immunosuppression. Results: The infiltration of CD68+ macrophages in the interstitium increased in patients with LN. High levels of CD68+ macrophage infiltration in the interstitium were associated with a low probability of treatment response in the adjusted analysis, and verse vice. The density of CD68+ macrophage infiltration in the interstitium alone predicted the response to immunosuppression (area under the curve [AUC], 0.70; 95% CI, 0.63 to 0.76). The addition of CD68+cells/interstitial field to the pathological and clinical data at biopsy in the prediction model resulted in an increased AUC of 0.78 (95% CI, 0.73 to 0.84). Conclusion: The density of tubulointerstitial macrophage infiltration is an independent predictor for treatment response in LN. Adding tubulointerstitial macrophage infiltration density to clinicopathological data at the time of biopsy significantly improves risk prediction of treatment response in LN patients.

Potential involvement of circulating exosomal miRNA-146a in disease activity and TRAF6 gene expression in juvenile proliferative lupus nephritis.

BACKGROUND: Juvenile SLE (JSLE) is a complex autoimmune disorder that predominantly affects children and adolescents with several unique challenges, and microRNA-146a (miRNA-146a) might be an interesting anti-inflammatory molecule. Because exosomes in the blood might protect miRNAs, the association between circulating exosomal miRNA-146a and lupus proinflammatory genes, such as IRAK1 and TRAF6, was studied in peripheral blood mononuclear cells from people with JSLE. METHODS: Blood samples from 12 patients were collected every 3 months until 1 year with the recorded disease activity, and quantitative real-time PCR was used to determine the circulating exosomal miRNA-146a and the gene expression (IRAK1 and TRAF6). RESULTS: The mean age was 12.60±0.43 years at diagnosis and all patients had a complete response at 12 months. According to the nanoparticle tracking analysis, the abundance of exosomes was significantly lower at 3, 6 and 12 months compared with 0 months, while the level of circulating exosomal miRNA-146a was significantly higher at 12 months than at diagnosis (p<0.001). There was a negative correlation between the level of circulating exosomal miRNA-146a expression and the level of TRAF6 mRNA (r=-0.30, p=0.049). Moreover, there were correlations between circulating exosomal miRNA-146a and disease severity such as SLE Disease Activity Index 2000 score, anti-double-stranded DNA antibody and proteinuria (urine protein-creatinine ratio), respectively. Therefore, increasing the level of circulating exosomal miRNA-146a, which might control TRAF6 mRNA expression, could have an effect on the production of inflammatory cytokines. CONCLUSION: This suggests that miRNA-146a might serve as a non-invasive biomarker to evaluate the response to treatment in patients with juvenile lupus nephritis.

Population-wide long-term study of incidence, renal failure, and mortality rates for lupus nephritis.

OBJECTIVE: Given limited regional data, we investigate the state-wide epidemiology, renal and patient outcomes for lupus nephritis (LN) in Western Australia (WA). METHODS: Patients hospitalized with incident SLE (≥2 diagnostic codes in the state-wide WA Health Hospital Morbidity Data Collection) in the period 1985-2015 were included (n = 1480). LN was defined by the presence of glomerulonephritis and/or raised serum creatinine. Trends over three study decades for annual incidence rate (AIR)/100.000 population, mortality (MR), and end-stage renal disease (ESRD) rates/100 person years were analyzed by least square regression and compared with a matched control group (n = 12 840). RESULTS: Clinical evidence of LN developed in 366 SLE patients (25.9%) after a median disease duration of 10 months (IQR 0-101) with renal biopsy performed in 308 (84.2%). The AIR for LN (0.63/100.000) did not change significantly over time (R2 = .11, p = .85), while point prevalence reached 11.9/100.000 in 2015. ESRD developed in 14.1% (n = 54) of LN patients vs. 0.2% in non-LN SLE patients and 0.05% in controls (all p ≤ 0.01). ESRD rates increased over time in LN patients (0.4 to 0.7, R2 = .52, p = .26). The odds ratio for death was 8.81 (CI 3.78-22.9) for LN and 6.62 (CI 2.76-17.9) for non-LN SLE patients compared to controls and MR for LN patients increased over time (1.3 to 2.2, R2 = .84, p = .26). CONCLUSIONS: The incidence rate of LN in WA remained unchanged over 30 years. A lack of improvement in renal failure and mortality rates illustrates the pressing need for better long-term treatment options and/or strategies in LN.

Rationale and design of the Japanese Biomarkers in Nephrotic Syndrome (J-MARINE) study.

INTRODUCTION: Disease subtyping and monitoring are essential for the management of nephrotic syndrome (NS). Although various biomarkers for NS have been reported, their clinical efficacy has not been comprehensively validated in adult Japanese patients. METHODS: The Japanese Biomarkers in Nephrotic Syndrome (J-MARINE) study is a nationwide, multicenter, and prospective cohort study in Japan, enrolling adult (≥18 years) patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), membranoproliferative glomerulonephritis (MPGN), C3 glomerulopathy (C3G), and lupus nephritis (LN). Baseline clinical information and plasma and urine samples will be collected at the time of immunosuppressive therapy initiation or biopsy. Follow-up data and plasma and urine samples will be collected longitudinally based on the designated protocols. Candidate biomarkers will be measured: CD80, cytotoxic T-lymphocyte antigen 4, and soluble urokinase plasminogen activator receptor for MCD and FSGS; anti-phospholipase A2 receptor and thrombospondin type-1 domain-containing protein 7A antibodies for MN; fragment Ba, C3a, factor I, and properdin for MPGN/C3G; and CD11b, CD16b, and CD163 for LN. Outcomes include complete and partial remission, relapse of proteinuria, a 30% reduction in estimated glomerular filtration rate (eGFR), eGFR decline, and initiation of renal replacement therapy. The diagnostic accuracy and predictive ability for clinical outcomes will be assessed for each biomarker. RESULTS: From April 2019 to April 2023, 365 patients were enrolled: 145, 21, 138, 10, and 51 cases of MCD, FSGS, MN, MPGN/C3G, and LN, respectively. CONCLUSION: This study will provide valuable insights into biomarkers for NS and serve as a biorepository for future studies.

Lupus Nephritis Biomarkers: A Critical Review.

Lupus nephritis (LN), a major complication in individuals diagnosed with systemic lupus erythematosus, substantially increases morbidity and mortality. Despite marked improvements in the survival of patients with severe LN over the past 50 years, complete clinical remission after immunosuppressive therapy is achieved in only half of the patients. Therefore, timely detection of LN is vital for initiating prompt therapeutic interventions and improving patient outcomes. Biomarkers have emerged as valuable tools for LN detection and monitoring; however, the complex role of these biomarkers in LN pathogenesis remains unclear. Renal biopsy remains the gold standard for the identification of the histological phenotypes of LN and guides disease management. However, the molecular pathophysiology of specific renal lesions remains poorly understood. In this review, we provide a critical, up-to-date overview of the latest developments in the field of LN biomarkers.

Monogenic systemic lupus erythematosus onset in a 13-year-old boy with Noonan like-syndrome: a case report and literature review.

BACKGROUND: Childhood systemic lupus erythematosus (cSLE) has been considered as a polygenic autoimmune disease; however, a monogenic lupus-like phenotype is emerging with the recent recognition of several related novel high-penetrance genetic variants. RASopathies, a group of disorders caused by mutations in the RAS/MAPK pathway, have been recently described as a cause of monogenic lupus. CASE PRESENTATION: We present a 13-year-old boy with Noonan-like syndrome with loose anagen hair who developed a monogenic lupus. The renal biopsy confirmed a class III lupus nephritis and identified the presence of zebra bodies. CONCLUSIONS: RASopathies represent a cause of monogenic lupus. We report a new case of monogenic lupus in a child with Noonan-like syndrome with loose anagen hair. Lupus nephritis which has never been described in this context, may be part of the presentation. The presence of zebra bodies in SLE or RASopathies in unclear, but no other known conditions (Fabry disease or drugs) were identified as the cause of zebra bodies in our patient.

Complement C4d as a biomarker for systemic lupus erythematosus and lupus nephritis.

Background: Increasing studies in the last decade have led to the widespread understanding that C4d, a split product of complement component 4 (C4), is a potential biomarker for systemic lupus erythematosus (SLE) and lupus nephritis (LN).Purpose: The aim of this review is to summarize the highlights of studies investigating the use of C4d as a biomarker for diagnosing and monitoring SLE and LN patients.Data collection: we searched PubMed/Medline and Wanfang databases using the terms "C4d and systemic lupus erythematosus", "C4d and lupus nephritis", and "Complement C4d".Results: The deposition of C4d on circulating blood cells has been shown in several clinical studies to be a potential diagnostic marker that can be used to monitor patients with SLE. In addition, C4d deposits on circulating blood cells may be a helpful diagnostic marker for LN, one of the most severe complications of SLE. Meanwhile, studies utilizing renal biopsy specimens have indicated that C4d deposition in the renal peritubular capillaries of LN patients may predict more severe LN or a worse patient prognosis. Generally, a high plasma C4d level and a high plasma C4d/C4 ratio may also be promising indicators that can be used to monitor patients with SLE and LN.Conclusions: C4d detection may be a novel strategy for further clinical prediction and therapy.

The role of urinary biomarker monocyte chemoattractant protein (MCP-1) in correlation with different histopathological classes of lupus nephritis in Egyptian patients.

Lupus nephritis (LN) affects almost two-thirds of systemic lupus erythematosus (SLE) patients. Renal biopsy is the gold standard for the diagnosis of LN. However, repeated biopsies are not always performed in clinical practice, and they carry some risk. Therefore, minimally invasive techniques, as urinary biomarkers, are promising tools for the diagnosis and monitoring of SLE. Previous studies evaluated urinary monocyte chemoattractant protein-1 (MCP-1) in patients with SLE, reported higher levels of urinary MCP-1 in patients with active LN than non-active LN. Other studies reported higher levels of urinary MCP-1 in LN patients with proliferative forms (III and IV). This study aimed to evaluate urinary MCP-1 as a noninvasive diagnostic biomarker tool for LN, and to determine its association with different LN histopathological stages and chronicity indices. The study included 40 SLE patients with biopsy-proven LN class II, III, IV or V, and 20 patients with inactive LN as a control group. In LN active patients, the mean creatinine was 1.71 ± 0.55 mg/dl, and 0.84 ± 0.10 mg/dl in the control group. The mean MCP-1 level was 618.4 ± 294.2 ng/l in active LN patients and 120.05 ± 87.53 ng/l in inactive LN patients. The receiver operating characteristic (ROC) curve analysis indicated a better diagnostic performance of MCP-1 than conventional biomarkers. At area under the curve of 0.990, the best cut-off level was >245 ng/L (sensitivity 97.5 %, Specificity 95 %). In conclusion, urinary MCP-1 distinguished active LN from inactive renal disease. It can be proposed as a good noninvasive diagnostic biomarker with a high sensitivity and specificity for detection of LN activity..

Urinary tissue factor (uTF), tissue factor pathway inhibitor (TFPI) and plasmin as novel biomarkers in early diagnosis of lupus nephritis.

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease, with multi systematic affection. Lupus nephritis (LN) is the most frequent cause of renal damage in SLE patients with variable presentations that may progress to end stage renal failure. Coagulation disorders are frequently reported in SLE and LN with higher mortality rates. Renal biopsy is an invasive process, and the existing indicators for LN diagnosis and activity are unreliable. New urinary biomarkers with significant validity, safety, and accuracy are the current focus of most studies. Our study sought to assess the value of urinary tissue factor (uTF), tissue factor pathway inhibitor (TFPI), and plasmin as biomarkers for the early identification and detection of LN and its activity. This was a cross-sectional study, included 100 subjects (80 SLE patients, and 20 healthy controls), they were recruited from the Internal Medicine department, Rheumatology and Nephrology units and outpatient's clinics at Assiut University hospital between the period of 2020 and 2022. All patients underwent full history taking, clinical evaluation, and activity scoring calculation and laboratory investigations. The results showed that the best diagnostic accuracy of LN was observed with TFPI (90% accuracy, sensitivity 80% and specificity 95% with p <0.001 at cutoff point of >193.2 ng/ml), followed by uTF (75.4% overall accuracy at cut off point of >12.6 ng/ml, sensitivity 90% and specificity 68% with p < 0.001) and plasmin (70.3% accuracy at cut off point of >30.5 ng/ml, sensitivity 55% and specificity 78% with p < 0.001). Urinary TFPI was the best predictor of LN occurrence with odd ratio of 4.34, (p < 0.001). In conclusion urinary TFPI could be used as a diagnostic marker for LN with high accuracy and an early predictor of LN.

Pregnancy Outcomes in a Diverse US Lupus Cohort.

OBJECTIVE: Although the population of patients with systemic lupus erythematosus (SLE) is racially and ethnically diverse, many study populations are homogeneous. Further, data are often lacking on critical factors, such as antiphospholipid antibodies (aPLs). We investigated live birth rates in patients with SLE at Kaiser Permanente Northern California, including race and ethnicity and aPL data. METHODS: Electronic health records of pregnancies with outcomes observed from 2011 to 2020 were identified among patients with SLE. Prevalent SLE was defined as two or more International Classification of Diseases-coded visits seven or more days apart before the last menstrual period. We summarized patient characteristics, medication orders, health care use, and medication use. Pregnancy outcomes (live birth, stillbirth, spontaneous abortion, ectopic pregnancy, and molar pregnancy) were presented overall and stratified by race and ethnicity, aPL status, and nephritis history. RESULTS: We identified 657 pregnancies among 453 patients with SLE. The cohort was diverse, reflecting the Northern California population (27% Asian, 26% Hispanic, 26% Non-Hispanic White, 13% Non-Hispanic Black, 5% multiracial, and approximately 2% Pacific Islander and Native American). Approximately 74% of observed pregnancies ended in live birth, 23% resulted in spontaneous abortion, 2% were ectopic or molar pregnancies, and <1% were stillbirths. There was limited variability in live births by race and ethnic group (72%-79%), aPL status (69.5%-77%), and nephritis history (71%-75%). CONCLUSION: Our findings are consistent with previous studies; however, some methodologic differences may yield a range of live birth rates. We found that approximately 74% of pregnancies in patients with SLE ended in live birth, with modest variability in spontaneous abortion by race and ethnicity, nephritis history, and aPL status.

A nomogram predicting the histologic activity of lupus nephritis from clinical parameters.

BACKGROUND: The 2021 clinical guidelines of the Kidney Disease: Improving Global Outcomes emphasize the importance of the histological activity index (AI) in the management of lupus nephritis (LN). Patients with LN and a high AI have poor renal outcomes and high rates of nephritic relapse. In this study we constructed prediction models for the AI in LN. METHODS: The study population comprised 337 patients diagnosed with LN using kidney biopsy. The participants were randomly divided into training and testing cohorts. They were further divided into high-activity (AI >2) and low-activity (AI ≤2) groups. This study developed two clinical prediction models using logistic regression and least absolute shrinkage and selection operator (LASSO) analyses with laboratory test results collected at the time of kidney biopsy. The performance of models was assessed using 5-fold cross-validation and validated in the testing cohort. A nomogram for individual assessment was constructed based on the preferable model. RESULTS: Multivariate analysis showed that higher mean arterial pressure, lower estimated glomerular filtration rate, lower complement 3 level, higher urinary erythrocytes count and anti-double-stranded DNA seropositivity were independent risk factors for high histologic activity in LN. Both models performed well in the testing cohort regarding the discriminatory ability to identify patients with an AI >2. The average area under the curve of 5-fold cross-validation was 0.855 in the logistic model and 0.896 in the LASSO model. A webtool based on the LASSO model was created for clinicians to enter baseline clinical parameters to produce a probability score of an AI >2. CONCLUSIONS: The established nomogram provides a quantitative auxiliary tool for distinguishing LN patients with a high AI and helps physicians make clinical decisions in their comprehensive assessment.

Elevated serum uric acid is associated with renal arteriolopathy and predict poor outcome in patients with lupus nephritis.

OBJECTIVES: Increased serum uric acid (SUA) levels are well known to be concomitant of cardiovascular and kidney diseases, and have been proposed to be implicated in the development of arteriolar damage. The aim of the present study was to assess the association between SUA levels, renal damage and its implication for outcome in patients with lupus nephritis (LN). METHODS: This retrospective study included 194 cases with biopsy proven LN at the Affiliated Hospital of Qingdao University between January 2013 and June 2021. We reviewed clinical, laboratory and histologic data of patients and analysed the correlation between SUA levels, renal damage and the primary outcome (death or ESRD). Biopsy-proven arteriolar damage was defined by the presence of arteriolar hyalinosis and/or intimal thickening. RESULTS: Compared to LN patients without hyperuricemia, LN patients with hyperuricaemia presented with higher BP, hyperlipidaemia, lower eGFR, lower haemoglobin, lower serum albumin, worse renal arteriolar damage and proteinuria, and also higher SLEDAI score, activity index and chronicity index (p<0.05). At logistic regression analysis, SUA was independently related to the presence of arteriolar damage. For each 100 µmol/L increase in SUA levels the risk for arteriolar damage raised by 53.8% (hazard ratio [HR] =1.538; 95% CI: 1.147-2.063; p=0.004) after adjustment for haemoglobin, serum creatinine and erythrocyte sedimentation rate. Cox regression analysis showed that female (HR=3.180; 95% CI: 1.216-8.313; p=0.018), white blood cell count (HR=1.111; 95% CI: 1.027-1.202; p=0.009), SUA (HR=1.100; 95% CI: 1.023-1.253; p=0.035), serum creatinine (HR=1.800; 95% CI: 1.348-2.404; p<0.001), and renal arteriolar damage (HR=3.117; 95% CI: 1.022-9.511; p=0.046) was significantly associated with development of ESRD or death in patients with LN after adjustment for several potential confounding factors. Furthermore, for each 100 µmol/L increase in SUA levels, the risk of ESRD or death increased by 10%. CONCLUSIONS: SUA levels are directly associated with renal arteriolar damage and poor prognosis in LN patients. Hyperuricaemia is an important predictor for poor prognosis in patients with LN.

Levels of Proteinuria and Renal Pathology in Systemic Lupus Erythematosus Patients.

According to the current guidelines, renal biopsies are performed in systemic lupus erythematosus (SLE) patients for proteinuria of 0.5 g/24 h or higher. Renal pathology may be present in patients with lower-level proteinuria (<0.5 g/24 h). We aimed to review the renal histopathology in SLE patients, with lower levels of proteinuria. In this retrospective study, we retrieved SLE patients' data, including 24-h urinary protein excretion and renal histopathology results. We compared various parameters in different lupus nephritis (LN) classes and in different levels of proteinuria (urinary protein <0.5 g, 0.5 to <1 g, and ≥1 g per 24 h). Out of 476 patients, 274 (57.6%) had proteinuria of <0.5 g, 44 (9.2%) had 0.5 to <1 g, and 158 (33.2%) had ≥1 g per 24 h. SLE patients with proteinuria of <0.5 g/24 h were found to have LN, including the proliferative classes. Of the 299 LN cases confirmed by a renal biopsy, low-level proteinuria (<0.5 g) was found in 39.8% of all LN patients, in 50% of patients with Class III LN, 33.3% of those with Class IV LN, 31.4% of those with Class V LN, and 41.4% of those with other LN classes (II/V, III/V, and IV/V). Overall, 35.9% (87/242) of patients with the proliferative LN classes (III, IV, V, II/V, III/V and IV/V) had low-level proteinuria of <0.5 g/24 h. SLE patients with low-level proteinuria had significant renal pathology. Our study suggests there is a need to perform renal biopsies at lower levels of proteinuria.

Polyneuritis cranialis as a unique initial presentation of juvenile systemic lupus erythematosus: Case report.

Cranial neuropathy is a rare presentation in juvenile (j) SLE and being multiple is even rarer. We describe here an adolescent girl presenting with polyneuritis cranialis (PNC) as an initial presentation of SLE which had not been reported before in literature. She presented with symptoms suggestive of bilateral abducent and hypoglossal neuropathy with nerve conduction studies showing partial axonal neuropathy of left facial and accessory nerves, 6 weeks after common cold. The condition was not associated with any other neurological or systemic manifestations nor features of Sjogren's syndrome. Her condition responded well to pulsed methylprednisolone therapy and plasma exchange. After exclusion of the common causes and owing to the initial positive ANA results and mild proteinuria, renal biopsy was taken and revealed histopathological features of class III lupus nephritis for which mycophenolate mofetil was started at 1200 mg per m2. Our case highlights the importance of considering collagen disorders including SLE in the differential diagnosis of children presenting with PNC in order to allow adequate management and proper follow-up.

Lupus Nephritis Risk Factors and Biomarkers: An Update.

Lupus nephritis (LN) represents the most severe organ manifestation of systemic lupus erythematosus (SLE) in terms of morbidity and mortality. To reduce these risks, tremendous efforts have been made in the last decade to characterize the different steps of the disease and to develop biomarkers in order to better (i) unravel the pre-SLE stage (e.g., anti-nuclear antibodies and interferon signature); (ii) more timely initiation of therapy by improving early and accurate LN diagnosis (e.g., pathologic classification was revised); (iii) monitor disease activity and therapeutic response (e.g., recommendation to re-biopsy, new urinary biomarkers); (iv) prevent disease flares (e.g., serologic and urinary biomarkers); (v) mitigate the deterioration in the renal function; and (vi) reduce side effects with new therapeutic guidelines and novel therapies. However, progress is poor in terms of improvement with early death attributed to active SLE or infections, while later deaths are related to the chronicity of the disease and the use of toxic therapies. Consequently, an individualized treat-to-target strategy is mandatory, and for that, there is an unmet need to develop a set of accurate biomarkers to be used as the standard of care and adapted to each stage of the disease.

Infliximab biosimilar-induced lupus nephritis: A case report.

We present a case of microhematuria, proteinuria and hypocomplementemia which developed in a 55-year-old female who was being treated with an infliximab biosimilar for rheumatoid arthritis. Renal biopsy showed lupus nephritis (ISN/RPS classification class IV + V). Treatment with the infliximab biosimilar was discontinued, and treatment with prednisolone, hydroxychloroquine and abatacept was started, resulting in clinical remission of lupus nephritis and RA. Although tumour necrosis factor-α α inhibitors are known to induce production of autoantibodies, symptoms are usually limited to skin involvement or arthritis, and renal complications are rare. Physicians should be aware of the risk of lupus nephritis and carefully monitor patients for the development of renal involvement during treatment with tumour necrosis factor-α inhibitors.

Letter to the editor: testing the effectiveness of MyPROSLE in classifying patients with lupus nephritis.

Because of the clinical heterogeneity among patients with systemic lupus erythematosus (SLE), developing molecular profiles that predict clinical features can be useful in creating a personalized approach to treatment. Toro-Domínguez et al. created a web tool to aid in therapeutic decision making for clinicians that predicts clinical features associated with SLE from blood transcriptomic data. Specifically, they present a machine learning model that predicts the presence of proliferative nephritis from blood transcriptomics. Here, we report use of the tool in independent datasets and found that it did not perform sufficiently well to consider replacement of the standard kidney biopsy as a diagnostic procedure.